Fighting cancer with nanotechnology

Winners of the European Inventor Award 2013 in the category Research

In the fight against cancer, scientists have long dreamed of
a ‘magic bullet' to eliminate diseased cells without harming healthy tissue.
This dream became reality when nano-capsules that deliver potent anti-cancer
drugs directly to tumour sites entered clinical practice.

The revolutionary method is based on breakthrough
discoveries patented by Belgian-born nanotechnology pioneer Patrick Couvreur,
Professor and Director of the Physical Chemistry, Pharmacotechnology and
Biopharmacy Unit at Paris-Sud University in France.

Treating a top
killer

Despite
advancements in treatment, cancer remains one of the leading causes of death
worldwide. And it's getting worse: In the year 2030, researchers from the
International Agency for Research on Cancer (IARC) expect 22.2 million new
cases of cancer worldwide, a 75% rise from 2008.

Chemotherapy,
the treatment of cancer with toxic chemicals suppressing the multiplication of
diseased cells, is one of the main weapons against the disease.

Chemotherapy had its start in the early 1900s, and its
underlying principle has always remained the same: The aggressive chemicals
trigger the death of fast-dividing cells such as the ones involved in cancer.

But chemotherapy's side effects can be devastating because
it doesn't only harm tumours but can also wreak havoc on healthy cells in the
patient's liver, digestive tract and bone marrow. And the right dosage is key: The
difference between poison and cure was often in the realm of a few milligrams.

“Pharmaceutical companies are extremely aware of a clear and focused patent situation before investing into development or production.”

A ‘magic
bullet' for targeting cancers

Looking for an alternative, the ‘father' of chemotherapy,
1908 Nobel Laureate for Medicine Paul Ehrlich, envisioned a more controlled way
of killing diseased cells. The pioneer dreamed of drugs that would hit home
like magic bullets, called ‘Zauberkugeln' in German - never missing their
intended target.

The magic bullets remained a dream until the year 1977, when
nanotechnology pioneer Professor Peter Paul Speiser met young researcher
Patrick Couvreur at the ETH (Swiss Federal Institute of Technology) in Zurich.

Together, the two pursued the fundamental principle of
today's nano-medicines: By sealing the active ingredients inside nano-capsules
- miniature materials that gradually break down after injection - the drugs
take effect in a prolonged, more controlled manner. Adverse side effects are
also reduced.

The long road
to scientific breakthroughs

In 1979, Couvreur succeeded in encapsulating medicines in biodegradable
nano-particles, making them fit for use in humans - in theory, at least.

To keep things moving, Couvreur took his research to
Paris-Sud University, where he assumed key responsibilities as a researcher and
coordinator between academics and the pharmaceutical industry.

In order to carry out clinical trials of his invention,
Couvreur founded Paris-based BioAlliance company in 1997. One initial challenge
was to scale up the production of nano-particles: "During laboratory research,
we were working with milligrams, for the clinical phase we needed kilograms,"
Couvreur said.

Securing a European patent was also key in getting the new
company off the ground: "Pharmaceutical companies are extremely aware of a
clear and focused patent situation before investing into development or
production," Couvreur said.

“At the moment, we are already able to optimise the ratio of drug transporter and drug agent by 50 times. Let’s see where we will stand in a few years.”

Bridging the
gap between research and practice

Since its founding in 1997, Couvreur's company BioAlliance
Pharma has raised €20.8 ($27.0) million from financial and strategic investors.
Current results are highly promising:

"At the moment, we are already able to optimise the ratio of
drug transporter and drug agent by 50 times. Let's see where we will stand in a
few years," Couvreur said.

The pioneer's nano-medicines are especially suitable for the
treatment of pancreatic cancer, a drug market expected to exceed $1.5 billion
by 2015. In Europe, pancreatic cancer is the 10th most frequent cancer type,
accounting for 2.6% of cancer in both sexes, and the eighth leading cause of
cancer-related death, with approximately 65,000 deaths each year.

"We are attacking other diseases. One important disease is
HIV. Our first tests were extremely encouraging that our nano-capsules will
also increase the efficiency of drug delivery for HIV treatment," said
Couvreur.

Dreaming of a
‘drug discovery institute'

Constantly striving to see medical breakthroughs all the way into clinical practice, Patrick Couvreur cofounded the Therapeutics Innovation doctoral school at Paris-Sud University, where he was from 1998 to 2010 director of the Physical Chemistry, Pharmacotechnology and Biopharmacy Unit with a team of 110 researchers.

"My real dream is to develop an effective anti-cancer
medicine and to create a 'drug discovery institute' in the
Ile-de-France region, to give France international visibility in
this field," Couvreur said.

A lifetime of
dedication to research

Together with his research team at start-up company
Medsqual, Couvreur is currently working on the third generation of
nano-particles. It combines the anti-cancer drug Gemcitabine with the compact
lipid squalene for a ten-fold increase in effectiveness on tumours. The new
drug was patented in 2011 and is now undergoing Phase III clinical trials, with
expected approval by FDA and EU regulators by 2015/2016.

With his dedication to research and constant lobbying in the
pharmaceutical industry, Patrick Couvreur has played a key role in fulfilling
the dream of magic bullets envisioned by pioneer Paul Ehrlich more than 100
years ago.

How it works

The nano-particles
invented by Patrick Couvreur measure between only 10 to 1,000 nanometres and
are free to travel throughout the body without being absorbed or dissolved like
conventional drugs injected into the bloodstream.

Instead of releasing
their biologically active ingredients right after injection, the drugs inside
nano-capsules only deliver their load after the outside coating has dissolved,
either because of changes in temperature or of chemical factors such as the
biological breakdown of fats in certain body regions.

As a result,
nano-capsules offer a much longer half-life in the bloodstream compared to
conventional injections, and they can take effect in a much more concentrated,
spatially condensed fashion.

Another advantage of
covering drugs with polymers lies in the fact that the human immune system does
not recognise the drug before the coating is dissolved. Together with their
small size, this ‘stealth' coating enables drug-laden nano-particles to travel
throughout the body, even crossing the blood-brain barrier.

Science fiction, nano-robots and ‘remote-controlled' drugs

Before it advanced into
a billion-dollar market (expected to exceed $30 billion by 2015),
nanotechnology was the stuff of science fiction movies. In the 1966 film Fantastic Voyage, a team of researchers
is shrunk to nano-dimensions and injected into a person's blood stream. Medical
schools would screen the film to illustrate concepts of immunology.

Today, researchers
are fervently pursuing the construction of nanorobots, tiny machines at a scale
between 0.1 and 10 micrometres. In the future, these micro-machines could be
injected into patients to fulfil a number of tasks, from diagnostic surveys to the
repairing of cells all the way to nano-surgery.

Another cutting-edge
approach to controlled drug delivery lies in the combination of nano-particles
with magnetic nano-crystals, which can be ‘remote-controlled' via
high-resonance magnetic fields to targeted locations inside the human body.

Potent anti-cancer
drugs are in higher demand than ever before. Cancer is currently the leading
cause of death worldwide, and the World Health Organization estimates its toll
to rise to 13.1 million in 2030.